Pulmonary embolism (PE), the most serious form of venous thromboembolism (VTE), is a leading cause of maternal mortality in the developed world. Maternal mortality is a devastating event with far-reaching emotional, social and economic implications. Symptomatic VTE is estimated to occur antepartum in 5-12 per 10,000 pregnancies, and to occur postpartum in 3-7 per 10,000 deliveries. Compared with age-matched, non- pregnant controls, this translates into a per day risk that is increased 7-10 fold for antepartum VTE, and 15-35 fold for postpartum VTE. Hence, the postpartum period is the period of greatest risk. The important question of how best to prevent pregnancy-related VTE remains unanswered, in part because it has been difficult to identify otherwise young and otherwise healthy women who are at high risk for VTE. However, a recent large, well-conducted case control study identified risk factors in postpartum women, including factors, when combined, which resulted in multiplicative effect. Based on these data, we can define a group of women with OR >10 for post-partum VTE. We hypothesize that targeted VTE prophylaxis in the early post-partum period will result in a significant decrease in symptomatic deep vein thrombosis (DVT) and PE and asymptomatic proximal DVT. Targeted post-partum prophylaxis could impact >25% of deliveries in the U.S. and Canada and significantly change obstetric care. A randomized trial to assess the efficacy of VTE prophylaxis in this setting is needed. Important questions regarding the feasibility of such a trial need to be addressed prior to embarking on a definitive trial. This application outlines a feasibility study with the following Specific Aims: 1) To enroll women at risk (OR>10) of post-partum VTE, without other indications for VTE prophylaxis, in a randomized controlled trial of prophylactic LMWH versus placebo, beginning within 36 hours post-partum and continuing for 3 weeks at 3 participating institutions, 2) To assess our prediction that at least 30% of eligible women approached will agree to enroll, at least 80% of women will comply with study drug injections, and at least 90% will have an evaluable ultrasound at end of study, 3) To assess the acceptance of a placebo injection arm in this setting, and 4) To finalize a multi-center trial based on the findings of this pilot/feasibility study. PUBLIC HEALTH RELEVANCE: Venous thromboembolism (VTE) including deep venous thrombosis and pulmonary embolism are major contributors to maternal morbidity and mortality in the U.S. This study aims to determine the feasibility of a trial to assess low molecular weight heparin prophylaxis in this setting, in order to decrease the incidence of post-partumVTE and associated illness and death.